Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies

The Lancet Respiratory Medicine, Год журнала: 2024, Номер 12(4), С. 323 - 336

Опубликована: Фев. 23, 2024

Язык: Английский

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The Impact of Immune System Aging on Infectious Diseases

Microorganisms, Год журнала: 2024, Номер 12(4), С. 775 - 775

Опубликована: Апрель 11, 2024

Immune system aging is becoming a field of increasing public health interest because prolonged life expectancy, which not paralleled by an increase in expectancy. As age progresses, innate and adaptive immune systems undergo changes, are defined, respectively, as inflammaging senescence. A wealth available data demonstrates that these two conditions closely linked, leading to greater vulnerability elderly subjects viral, bacterial, opportunistic infections well lower post-vaccination protection. To face this novel scenario, in-depth assessment the players involved changing epidemiology demanded regarding individual concerted involvement cells mediators within endogenous exogenous factors co-morbidities. This review provides overall updated description changes affecting system, may be help understanding underlying mechanisms associated with main age-associated infectious diseases.

Язык: Английский

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A unified metric of human immune health

Nature Medicine, Год журнала: 2024, Номер 30(9), С. 2461 - 2472

Опубликована: Июль 3, 2024

Язык: Английский

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Demographics and clinical characteristics of a new population of centenarians in Colombia. The COOLCEN cohort

Archives of Gerontology and Geriatrics Plus, Год журнала: 2024, Номер 1(1), С. 100006 - 100006

Опубликована: Янв. 8, 2024

Centenarians represent a successful model of biological aging that is becoming increasingly common but still largely unknown. Data about centenarians in Colombia scarce. The aim this study was to provide description the demographic and clinical characteristics new cohort Colombia. A retrospective, population-based undertaken, employing nationally validated registry provided by health insurance company. Demographic information prevalence rates significant chronic diseases were evaluated. geographical distribution at national level mapped. then compared with other age groups (>18-59 60-99 years-old), previous descriptions centenarians. Among 2,362,436 persons included study, 0.12% observed, which 50.7% female majority resides urban areas (64.9%). Chronic observed 275 (9.27%) centenarians, whom 113 (3.81%) disclosed one disease 162 (5.46%) multimorbidity. most prevalent essential hypertension (8.6%), kidney (4.4%), significantly lower others groups. free hematological, inflammatory arthritis, tuberculosis human immunodeficiency virus infections. COVID-19 2% cases. Significant differences outcomes assessed seen when comparing our results from previously described blue zones. COOLCEN discloses low age-related diseases, economic status no difference gender distribution. will valuable insights into healthy aging, prevention, improving well-being older adults.

Язык: Английский

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Vitamin D and Aging: Central Role of Immunocompetence

Nutrients, Год журнала: 2024, Номер 16(3), С. 398 - 398

Опубликована: Янв. 30, 2024

The pro-hormone vitamin D3 is an important modulator of both innate and adaptive immunity since its biologically active metabolite 1α,25-dihydroxyvitamin (1,25(OH)2D3) regulates via the transcription factor VDR (vitamin D receptor) epigenome transcriptome human immune cells controls in this way expression hundreds target genes. Since myeloid linage hematopoiesis epigenetically programmed by concert with pioneer factors PU.1 (purine-rich box 1) CEBPα (CCAAT/enhancer binding protein α), monocytes, macrophages, dendritic are most D-sensitive cell types. central role system various aging-related diseases suggests that immunocompetence describes not only ability individual to resist pathogens parasites but also contest non-communicative process aging itself. In review, we argue individual-specific responsiveness relates a person’s epigenetic programming function ligand 1,25(OH)2D3 during as well periphery. This may provide mechanism explaining how protects against major common and, parallel, promotes healthy aging.

Язык: Английский

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Disease Aggravation With Age in an Experimental Model of Multiple Sclerosis: Role of Immunosenescence

Aging Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

The onset of multiple sclerosis (MS) in older individuals correlates with a higher risk developing primary progressive MS, faster progression to secondary and increased disability accumulation. This phenomenon can be related age-related changes the immune system: age, system undergoes process called immunosenescence, characterized by decline function both innate adaptive responses. lead decreased ability control inflammation repair damaged tissue. Additionally, often experience shift toward more pro-inflammatory state, known as inflammaging, which exacerbate neurodegenerative diseases like MS. Therefore, alterations could responsible for difference phenotype MS observed younger patients. In this study, we investigated effects age on immunopathogenesis experimental autoimmune encephalomyelitis (EAE). Our findings indicate that EAE is severe aged mice due inflammatory environment central nervous system. Age-related predominantly affect immunity, altered T cell ratios, Th1 response, regulatory cells, exhaustion B antigen presentation, reduced NK maturation cytotoxicity. Transcriptomic analysis reveals fewer pathways transcription factors are activated EAE. These allow us identify potential therapeutic targets specific elderly patients work their development future.

Язык: Английский

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Intervention Approaches in Studying the Response to Vitamin D3 Supplementation

Nutrients, Год журнала: 2023, Номер 15(15), С. 3382 - 3382

Опубликована: Июль 29, 2023

Vitamin D intervention studies are designed to evaluate the impact of micronutrient vitamin D3 on health and disease. The appropriate design is essential for their quality, successful execution, interpretation. Randomized controlled trials (RCTs) considered “gold standard” studies. However, most recent large-scale (up 25,000 participants), long-term RCTs involving did not provide any statistically significant primary results. This may be because they similarly a therapeutic drug but nutritional compound that only limited set parameters per individual were determined. We propose an alternative concept using segregation study participants into different groups responsiveness supplementation in parallel measuring larger genome-wide over multiple time points. accordance with recently developed mechanistic modeling approaches do require large number participants, as case statistical results RCT. Our experience based VitDmet, VitDbol, VitDHiD, which allowed us distinguish high, mid, low responders. In particular, investigating vulnerable group responders will future more conclusive both clinical molecular benefits supplementation. conclusion, our approach suggests paradigm shift towards detailed investigations transcriptome epigenome-wide individuals, who, due longitudinal design, can act own controls.

Язык: Английский

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The 3 I’s of immunity and aging: immunosenescence, inflammaging, and immune resilience

Frontiers in Aging, Год журнала: 2024, Номер 5

Опубликована: Окт. 16, 2024

As we age, our immune system’s ability to effectively respond pathogens declines, a phenomenon known as immunosenescence. This age-related deterioration affects both innate and adaptive immunity, compromising function leading chronic inflammation that accelerates aging. Immunosenescence is characterized by alterations in cell populations impaired functionality, resulting increased susceptibility infections, diminished vaccine efficacy, higher prevalence of diseases. Chronic low-grade further exacerbates these issues, contributing decline overall health resilience. review delves into the characteristics immunosenescence examines various intrinsic extrinsic factors aging how hallmarks fates can play crucial role this process. Additionally, it discusses impact sex, social determinants, gut microbiota on aging, illustrating complex interplay altering function. Furthermore, concept resilience explored, focusing metrics for assessing identifying strategies enhance These include lifestyle interventions such diet, regular physical activity, stress management, use gerotherapeutics other approaches. Understanding mitigating effects are developing support robust responses aged individuals.

Язык: Английский

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Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales

Antibiotics, Год журнала: 2024, Номер 13(2), С. 185 - 185

Опубликована: Фев. 13, 2024

Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that resistant to meropenem but susceptible ertapenem, adding further complexity the clinical landscape. This study investigates emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 2018. The majority isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% all NCP had an ErMs phenotype. strains, E. comprised (72%). strains carrying blaCTX-M had, on average, 9-fold higher copies than CP-ErMs as well approximately 4-fold more blaCTX-M-positive ertapenem- (EsMs) (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed be mediated by harboring with without a carbapenemase(s). also carried mobile genetic elements, particularly IS26 composite transposons, EsMs (37 0.2, 0.0001). MGE- ISVsa5 uniquely abundant either or ErMr over 30 average counts both phenotype groups (p Immunoblot analysis demonstrated absence OmpC expression NCP-ErMs coli, 92% lacking full contig coverage ompC. Overall, our findings characterize collaborative independent efforts between indicating need reappraise term “non-carbapenemase (NCP)”, for highly expressing blaCTX-M. To improve outcomes CRE-infected patients, future should focus mechanisms underlying emerging subphenotype develop technologies its rapid detection provide targeted therapeutic strategies.

Язык: Английский

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Autoimmunity in centenarians. A paradox

Journal of Translational Autoimmunity, Год журнала: 2024, Номер 8, С. 100237 - 100237

Опубликована: Март 2, 2024

Autoimmune diseases (ADs) are one of the groups chronic illnesses that impose a significant burden disease and health costs worldwide. Age is crucial risk factor for onset ADs. Theoretically, it inferred with organic immune system aging, loss tolerance specificity activity becomes more intense, probability autoimmunity increasing. However, there group individuals whose prevalence ADs very low or non-existent, despite biological aging. This paradox in raises questions. Centenarians, who over 100 years old, possibly most successful model aging humans. Most these exhibit favorable phenotype. To date, primary data evidence potential hypotheses explaining this phenomenon lacking globally, even though could provide valuable, original, relevant information regarding understanding protective factors, drivers, biomarkers related to autoimmunity. Herein we discuss some hypothesis may explain absence centenarians, including inflammaging, immunosenescence resilience, hyperstimulation, proteodynamics, genetics.

Язык: Английский

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